Table 1.

Outcome measurements

Outcomes	Tool	Measurement strategy	Rationale
Primary outcome
Developmental delay	Bayley Scales of Infant and Toddler Development III (BSID III) The scale is used to assess language, cognitive, motor, social-emotional, and general adaptive functions	Assessment by Bayley-trained clinical psychologist/clinician between 24-and-36-month chronological age The BSID III scores will be calculated using corrected gestational age For the BSID III, the composite score range in different domains is as follows: Cognitive: 55–145 Language: 47–153 Motor: 46–154 Social-emotional: 55–145 Adaptive: 40–160 Composite score in each individual domain may be converted into scaled scores that range from 1 to 19. Average scaled scores are between 8 and 12 A composite score of < 80 will indicate developmental delay	BSID III has been developed in the USA and used in LMIC countries, including India [28–31] BSID III, in comparison to BSID II, requires a higher cutoff score for comparable sensitivity in detecting developmental delay. BSID III combined scores < 80 and cognitive and language scores < 85 were found to correlate with BSID II Mental Development Index (MDI) scores < 70 and clinically to moderate-severe developmental delay [31]
Cerebral palsy	Hammersmith Infant Neurological Examination (HINE)	Standardized neurological assessment using HINE at 6, 12, and 24 months According to a recent systematic review [32], HINE scores have 90% predictive accuracy of cerebral palsy By 12 months, a score of < 40 is predictive of non-ambulatory cerebral palsy [plegic, not walking] and a score of 40–60 is predictive of ambulatory cerebral palsy [able to walk], with any score < 70 considered abnormal. The maximum score is 78 The accepted norms will be used for the cutoff in this study, which are > 70 at 6 months and > 73 at 12 months and older [32–37] Due to the risk of more subtle findings, particularly in premature infants, there is increased sensitivity to the tool when used at multiple time points; therefore, the examination will be performed at an additional time point of 2 years For the primary outcome, the score at the 12- and 24-month assessments will be considered	HINE is a strongly recommended scale for early diagnosis of cerebral palsy [32] It is a standardized and scorable clinical neurological examination that is applicable for infants aged between 2 and 24 months and has been shown to be an easy-to-train tool with interobserver reliability even in less experienced staff [38]
Hearing impairment	Hearing assessment measured ideally at discharge or as soon as possible at enrolment or first follow-up	First assessment by screening auditory brainstem responses (ABR) If screening ABR is passed, no need for further hearing assessment tests In case screening ABR is failed, the participant is referred at the earliest possible opportunity to audiologist or specialist for re-screening, including, diagnostic ABR as applicable. Hearing impairment is defined as failed diagnostic ABR or failed re-screening ABR if diagnostic ABR is not available	International guidelines recommend hearing assessment within the first month of life whenever feasible [39] While Otoacoustic Emission (OAE) screening can be used in settings where ABR is not available, it is less preferred due to the potential for missing retro-cochlear hearing loss. Therefore, in studying high-risk infants, ABR is preferred [39–42]
Vision impairment	Structural visual examinations, including for retinopathy of prematurity, will be performed between discharge and 3 months, with visual acuity measured at 12 months	Visual acuity measured by Teller Acuity Cards at the facility Impairment defined by measurements 2 lines less than age-defined normative values	Teller Acuity Cards will be used due to the availability of age-specific reference ranges [43, 44]
Epilepsy	Screen for seizure at each follow-up visit. If screening positive, refer to a clinician	First assessment by epilepsy screening questionnaire at each follow-up visit If the participant screen negative, there is no need for further assessment tests In case the participant is screened positive, he/she will be assessed by a pediatrician/pediatric neurologist by a diagnostic questionnaire to arrive at a diagnosis of epilepsy/no epilepsy using the ILAE definition [45]. To reduce variability in diagnosis for purposes of this study, the ILAE diagnostic criterion has been operationalized for this study in the diagnostic questionnaire as either 2 unprovoked seizures separated by at least 24 h or 1 unprovoked seizure and one other positive finding of neurodevelopmental impairment	Screening questionnaires for pediatric epilepsy are limited due to small populations and limited age range and have demonstrated moderate validity [46, 47] A questionnaire comprised from validated pediatric epilepsy screening questionnaires and agreed upon by pediatric neurologists from the participating sites has been employed after local pilot testing
Secondary outcomes
Mortality	Screen for death of enrolled child occurring any time between 29 days and 3 years of age	Mortality/survival status at each screening point. Assessments performed every 3 months until the age of 3 years
Growth	Anthropometric parameters of weight (W), length (L), and head circumference (HC) for age using standardized equipment	Anthropometry at 6, 12, and 24 months of age. Parameters are plotted as per corrected age on WHO Multicentre Growth Reference Study (MGRS) charts and interpreted as per z scores Postnatal growth failure defined as fall in z scores or z scores < 2 SD	Measurements are obtained during facility visits. In case the participant is unable to visit the facility, we perform the measurement at the home of the participant
Feeding practices	Assessment of breastfeeding, expressed breast feeds, complementary feeds at 6 months, and adequacy of feeding beyond infancy	Feeding practices measured through a standard questionnaire at each follow-up visit—every 3 months until the age of 3 years
Maternal depression	Patient Health Questionnaire 9 (PHQ-9)	Maternal depression measured using PHQ-9 at 6 and 12 months of age	Literature suggests, while early screening for post-partum depression is important, additional screening points at either 6 or 12 months can capture additional women who may have initially screened negative at earlier time points. Therefore, we have included these time points in this study [48]
Home environment	HOME	Assessment of home environment measured using standard HOME-SF scale at 18 months by a home visit	HOME is a validated tool across cultures. The HOME-SF scale has 6 subscales: (1) parental responsivity, (2) acceptance of the child, (3) organization of the environment, (4) learning materials, (5) parental involvement, and (6) variety in experience These align with the MAL-ED study which has also identified that a three-factor structure—emotional and verbal responsivity, clean and safe environment, and child cleanliness—can be examined cross-culturally [49]